DESCRIPTION: Blood flow to active skeletal muscle increases dramatically during dynamic, whole body exercise. A long term goal of the proposed research is to determine the role of endothelium-dependent vasodilation in permitting increased muscle blood flow during exercise, in various types of skeletal muscle. In addition, the muscle blood flow response to exercise is blunted in various disease states and enhanced in the exercise trained state. Thus, another goal of the proposed research is to determine whether the contribution of endothelium-dependent vasodilation to exercise hyperemia is altered in these states. The experiments of Specific Aim 1 will test the hypothesis that high oxidative skeletal muscle exhibits potential for endothelium-dependent vasodilation in situ, and that this potential is utilized in increasing high oxidative muscle blood flow during muscle contractions. In addition, these experiments will test the hypothesis that nitric oxide is the primary mediator of endothelium-dependent vasodilation during muscle contractions. Experiments of Specific aim 2 will test the hypothesis that a period of chronically altered blood flow induces adaptations resulting in a change in potential for endothelium-dependent vasodilation. Altered vasodilatory potential is mediated primarily via changes in endothelial formation of nitric oxide. The experiments will be conducted in intact skeletal muscle in situ, and in isolated conductance and resistance arterial vessels. Finally, experiments of Specific Aim 3 will test the hypothesis that chronically induced alterations in potential for endothelium-dependent vasodilation are manifest during the hyperemia associated with muscle contractions. This comprehensive research program, ranging from the skeletal muscle microcirculation to the intact animals will improve our understanding of the cardiovascular response to exercise in health and disease.